Cancer is characterized by proliferation of abnormal cells. The success of conventional treatments depends on the type of cancer and the stage at which it is detected. Many treatments include costly and painful surgeries and chemotherapies and are often unsuccessful or only modestly prolong a patient's life. Promising treatment methods in development include tumor vaccines or T-cell therapy that target tumor antigens enabling a patient's immune system to differentiate between tumor and healthy cells and to elicit an immune response in the patient. See Chen, et al., Oncology Meets Immunology: The Cancer-Immunity Cycle, Immunity 39, Jul. 25, 2013, the contents of which are incorporated herein for all purposes in their entirety.
Neoantigens are a class of immunogens associated with tumor-specific mutations unique to a patient's cancer. Neoantigens have shown promise as targets for antitumor immunity techniques including adaptive T-cell transfer with tumor infiltrating lymphocytes (TIL), cancer vaccines, and checkpoint inhibitors. See Hacohen, et al., Getting Personal with Neoantigen-Based Therapeutic Cancer Vaccines, Cancer Immunol Res, Jul. 1, 2013, 11; Robbins, et al., Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells, Nature Medicine 19, 747-752 (2013); the contents of each of which are incorporated herein for all purposes in their entirety.
While strategies exist for identifying and prioritizing candidate neoantigens using sequenced tumor DNA and HLA typing, conventional techniques lack sensitivity and specificity, failing to identify some candidate neoantigens and providing unfocussed results that still require expensive validation procedures. Snyder, et al., Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma, N Engl J Med 2014; 371:2189-2199; Segal, et al., Epitope landscape in breast and colorectal cancer, Cancer Res. 2008 Feb. 1; 68(3):889-92; Fritsch, et al., 2014, HLA-Binding Properties of Tumor Neoepitopes in Humans, Cancer Immunol Res; 2(6); 1-8; the contents of each of which are incorporated herein for all purposes in their entirety.